Systems Biology Investigation of Cellular Senescence in Age-Related Human Disorders

Cellular senescence(definition) is a biologic mechanism, which is defined by irreversible cell cycle arrest and cellular dysfunction, and plays a role in aging and development of various age-related human diseases. There is growing evidence to show senescent cells contribute to chronic inflammation, tissue dysfunction, and degeneration via complicated molecular pathways and senescence-associated secretory phenotype (SASP). Nevertheless, the mechanism of cellular senescence at the systems level involving molecular processes involved in various human diseases has not been fully comprehended. The purpose of the study was to explore the molecular signatures and pathways of cellular senescence in human disorders with age using an integrative systems biology approach. Multi-omics datasets that are publicly available and relate to neurodegenerative, cardiovascular, metabolic, and musculoskeletal disorders were analyzed using differential gene expression profiling, construction of protein-protein interactions network, and functional enrichment analysis. Computational technologies such as network biology and pathway analysis were used to determine hub genes, pathways that have been dysregulated, and possible biomarkers associated with senescence. The findings showed that genes related to DNA repair response, inflammatory signal, oxidative stress response, p53 response, and mTOR(definition) activity vary significantly among various pathologies. A few hub genes and interconnected molecular networks were found as potential therapeutic targets. Comparative analysis revealed similar and disease-specific senescence signatures across age-related diseases. On the whole, the current study features a detailed systems-level understanding of the significance of cellular senescence in human conditions and identifies promising biomarkers and treatment points to be used as biomarkers and therapeutic targets in precision medicine and anti-aging efforts in the future.